Patient Education Blog

HIT = Heparin-induced Thrombocytopenia

What Is HIT?

Heparin-induced thrombocytopenia (HIT) is a serious side effect that may occur when you are being treated with heparin. It may lead to low blood platelet counts and to life-threatening blood clots. HIT is sometimes referred to as “heparin allergy”. However, it is not a true allergy.

Who Gets HIT?

Any patient who receives heparin can develop HIT. HIT occurs in about 2-3% of people who are treated with heparin and in less than 1% of people who are treated with low molecular-weight heparin (LMWH). The LMWH drugs that are available in the United States include dalteparin (Fragmin®), enoxaparin (Lovenox®), and tinzaparin (Innohep®). HIT is more likely to occur with use of higher doses of heparin, but HIT can also be caused by very small heparin doses, including the amount used to flush intravenous catheters.

What Is Heparin?

Heparin is a medication that is injected under the skin or into a vein to decrease clotting, or “thin the blood.” There are two forms of commonly used heparin: unfractionated and LMWH. These medications are used to prevent clots from forming or getting bigger. For patients who are bedridden in the hospital or who have had major surgery, heparin is often used to prevent clots from forming in the veins of the leg. It can also be used in the treatment of heart attack, stroke, deep vein thrombosis (blood clots in the deep veins of the legs or arms), or pulmonary embolus (blood clots in the lung).

What Causes HIT?

HIT is sometimes referred to as “heparin allergy”. However, this is not a correct term, as it is is not a true allergy. It is due to a kind of overreaction of a person’s immune system when he or she is given heparin. Normally, the body makes antibodies to protect us from infections. For unknown reasons, the immune system in some people makes antibodies in response to treatment with heparin (see Definitions, below). A small molecule within platelets called platelet factor-4 (PF4) is important in this process. The binding of the antibody to platelets activates them, so that they form clots at the wrong time or place. This can be harmful if the clots block blood flow to or from important parts of the body, such as the heart, brain, or a limb. After the antibodies bind to the platelets, they are removed together with the platelets from the blood stream, which can lead to a low platelet count. The medical term for a low platelet count is “thrombocytopenia”.

Definitions:

antibody: a special Y-shaped protein made by the body’s immune system, designed to work by binding to foreign substances (such as bacteria and viruses) to inactivate them or to mark them for removal by other parts of the immune system

platelet: a small cell-like particle in the bloodstream that helps stop bleeding by forming clots

What Problems Does HIT cause?

HIT leads to a low platelet count, but this usually does not lead to bleeding. Occasionally, however, bleeding in the brain (hemorrhagic stroke) and blood loss through the intestinal tract can occur. Non-heparin blood-thinning medicines (see table below in “How is HIT Treated?”) are often used to treat HIT and prevent blood clot(s) from forming or getting bigger. These medicines themselves may also increase the risk of bleeding.

If HIT is not recognized and treated, about 50% of patients with HIT develop serious or life-threatening blood clots, which can form in both arteries and veins. Arteries are blood vessels that carry oxygen-rich blood away from the heart to the body; veins return blood to the heart from the rest of the body. Clots that form in the arteries supplying blood to the brain and heart can cause strokes and heart attacks. HIT may also cause arterial clot formation in the arms and legs, leading to a loss of blood supply to these areas. This leads to gangrene (painful, cold, white extremity, which later turns black and may have to be amputated). Clots that form in veins can lead to deep venous thrombosis (DVT), which occurs in the deep veins of the legs, arms, or the abdomen. Clots can also occur in the blood vessels in the lung; this condition is called pulmonary embolism (PE). And clots can occur in blood vessels in the skin, leading to black and ulcerated skin lesions, called skin necrosis.

How Do I Know I Have HIT?

Although HIT is a serious medical condition and can even be fatal, you may feel well and have no worrisome symptoms even though HIT is developing within your body. Therefore, when you are receiving heparin, your health care providers must check your blood for platelet counts periodically. The exact schedule for testing should be determined by your health care provider.

Your doctor may suspect that you have HIT if your platelet count has fallen during heparin treatment and you have been receiving heparin for at least 5 days. If had already been treated with heparin in the previous 3 months, the platelet drop may occur more quickly. HIT usually leads to a fall in the platelet count of at least 50% of the pre-heparin value and/or to lower than the normal range. More rarely, HIT may be present even though the platelet count has decreased only very little, or not at all. HIT may also be suspected if you develop a new blood clot in spite of being on heparin. Your physician may use a scoring system called “4T score” to determine the likelihood of you having HIT (see table: HIT 4Ts). The 4 Ts refer to (1) Timing of the development of low platelets, (b) degree of Thrombocytopenia (i.e. degree of platelet decrease), (3) whether new Thrombosis (i.e. blood clot) has occurred during treatment with heparin, and (4) whether there is an alTernative reason for the low platelet count.

If HIT is suspected, testing for HIT should be done. The tests most commonly used in diagnosing HIT are:

PF4/heparin enzyme immunoassay (ELISA)

heparin-induced platelet aggregation assay

platelet serotonin release assay

Because the results of these tests take time to come back (up to several days in some cases), and because HIT requires rapid treatment, your health care providers may decide to treat you for HIT even if the testing has not been completed. In this instance, your health care providers may diagnose “possible” or “probable” HIT.

How Is HIT Treated?

Once HIT is suspected or diagnosed, treatment with all heparins – including LMWHs – must be stopped. In most cases, non-heparin blood thinners need to be given instead to prevent the formation or extension of blood clots (see table: HIT drugs). These medicines are usually given for at least 3-5 days, or until the platelet count has returned to the level it was at prior to treatment with heparin.

In addition to treatment with non-heparin blood thinners, your health care providers also may give you longer-term therapy with a “blood thinner”, such as warfarin (Coumadin®, Jantoven®). This gets started once the platelet count has increased to its baseline. Treatment with warfarin may be for a few weeks, a few months, or long-term, depending mostly on whether or not you have developed a blood clot.

In some cases, serious or life-threatening clots may require surgery to remove the clot or treatment with special clot-dissolving drugs. Unfortunately, serious complications still may develop, including loss of a limb, stroke, heart attack, or death. Because bleeding is rare in patients with HIT and the platelet count usually returns to the original level about 3-5 days after stopping heparin, platelet transfusions are typically not needed.

What Do I Need to Know?

If you have been diagnosed with HIT, you should inform all of your current and future health care providers that you have HIT.

If you have been diagnosed with HIT, you should not receive heparin in any form, unless advised to do so by your health care providers. This includes the LMWH drugs dalteparin (Fragmin®), enoxaparin (Lovenox®), and tinzaparin (Innohep®). In certain circumstances (such as during open-heart surgery) it may be o.k. for you to receive a few hours of heparin despite you having had HIT. However, this is a decision that only you and your health care providers can make.

Because blood clots due to HIT can form up to 6 weeks after your platelet count has returned to normal, it is very important that you remain on a protective blood thinner (such as warfarin) until your health care providers tell you to stop taking it. This medication requires close lab monitoring and frequent dose adjustments, so regular follow-up with your health care provider is essential.

You should wear a medical alert bracelet or necklace, or carry a wallet-card, saying “Heparin allergy – HIT”. You can ask your physician how to obtain one. You can also get one through a drug store or the Internet (e.g. www.medicalert.org and others).

Ask the healthcare provider who diagnoses you with HIT to fill out the “Patient History HIT” document included here (HIT: patient record). You can then provide this document to other health care providers who are currently or will be taking care of you.

The National Blood Clot Alliance (NBCA) website has information on clotting disorders and their treatment: www.stoptheclot.org.

A website maintained by the commercial suppliers of argatroban provides a webpage indicating frequently asked questions about HIT: www.argatroban.com/hit_faqs.htm

You can find informative articles on the Internet by searching for “heparin-induced thrombocytopenia” or “HIT” using your web search function. Be sure to consult with your health care provider about any information you find.

References

Note: The following articles were published in peer-reviewed medical journals and may include medical terminology that may not be familiar to most patients.

This blog entry was written by Dr. Tyler Buckner, Departments of Medicine and Pediatrics, and Dr. Stephan Moll, Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, NC.

Disclosures: Dr. Buckner and Dr. Moll have no financial conflict of interest with this blog entry.